The aim of this project is to explore several areas of fat metabolism related to energy homeostasis in normal and abnormal human newborns and in small mammals. Basic data obtained in normal fullterm infants show the capabilities of subcutaneous adipose tissue to change appropriately and meet varying needs during the first critical hours and days of life. Babies born after abnormal gestation or delivery, e.g. the prematurely, the small-for- gestational age infant, offspring of diabetic mothers, and those subjected to prolonged labor, fetal distress or hypoxia represent deviations from the usual transition to extrauterine life necessitating metabolic adaptation. Brown adipose tissue (BAT) in several mammalian species is known to be responible for a large part of "non-shivering" thermogenesis. Although only a limited amount of BAT has been found in human newborns, their thermoregulation is similar to that in small mammals. Special attention will be paid to the role of carnitine and its derivatives in the energy metabolism of developing WAT, BAT and muscle. The studies will be expanded to investigate the metabolism of free fatty acids and other substrates in the heart, muscle and brain of experimental animals. The talents, methodology and facilities of three groups of investigators will be combined to examine these problems: University of Miami, Fels Research Institute, and University of British Columbia. Samples of human adipose tissue (10 to 40mg) will be obtained by needle biopsy, tissue homogenates, fragments, isolated cells, or subcellular components and will be used to study respiratory mechanisms and their control, substrate transport and utilization, heat production, effects of hypoxia, and ultrastructural characteristics. Methods will include use of radioactive labeled substrates, biochemical tissue analysis, microcalorimetry, and light and electron microscopy. The groups of infants contribute greatly to neonatal morbidity and mortality. If metabolic abnormalities can be related to their disease states, the investigations provide the basis for the prevention or treatment of complications with subsequent reduction in perinatal morbidity and mortality.